Chemistry and Pharmacology Organic Chemistry pptx

Wash with water, then with dilute boric acid solution, then a drop of oil.. 22 RECREA TIONAL DRUGSrubber tubing to connect glass tubing \ Devices To Superheat Steam water condenser to va

TABLE OF CONTENTS

P r e f a c e 1

S a f e t y 4

Equipment, Technique and R e a g e n t s 7

Crystallization 10

Chromatography 15

D i s t i l l a t i o n 18

R e d u c t i o n s 3 0 A m p h e t a m i n e s 4 0 Hallucinogens 53

T H C s 7 0 Analgesics 85

Hypnotics, Sedatives And Tranquilizers 98

Buying P r e c u r s o r s 107

Making Precursors 1 1 5 The Work A r e a 131

Additional Information S o u r c e s 137

A b b r e v i a t i o n s 138

Chemical Sources N a t i o n w i d e 1 4 0 G l o s s a r y 142

Understanding The Periodic T a b l e 145

Miscellaneous T a b l e s 147

Preface 1

PREFACE

Congratulations You have just purchased the most complete and informative book on ational drug manufacture available It is based upon a great deal of experience and a tremendousamount of research I have used easy to understand terms to aid in comprehension of the formulasgiven and in the theory involved I have patterned this book after what would appear to be acollege textbook or a college accredited correspondence course in illicit drug manufacturing.Please follow carefully my instructions and advice on safety, purification, and referred to reading

recre-If you have any questions about even seemingly trivial details, then ask someone that knows.Call a college professor, an analytical laboratory, or one of the chemical consulting firms thatexist in metropolitan areas Aldrich Chemical Co has a toll free number (1-800-558-9160) thatenables you to ask the chemist on duty questions concerning what you may need to order fromthem and what cheaper analogs you may be able to substitute in the formula that you areinterested in Something that may appear to be insignificant may turn out to be the differencebetween completing or failing a formula and this chemist on duty gets paid to answer anyquestions you may have Do not be afraid to ask them (many other chemical suppliers have thistype of service also), but do not be a total idiot in doing this Use common sense, read up onyour subject thoroughly and then you will sound like a legitimate operation, not a clandestinedrug lab You will also be able to understand this person instead of having his educated talk go

in one ear and out the other Try not to let them realize what you're making, if possible, findanother use for the chemicals or reaction that is not illegal and tell them that is what you're doing.Never give a real name or address, if possible

Always put safety and caution before time, ease, and expense If these formulas can be carriedout by taking short cuts or by using cheaper reagents, then the scientists who invent them willexplain how to do them this way I have a total hatred towards underground chemists who rushout impure, improperly made drugs with unclean, half-assed equipment These people are notchemists at all and deserve to go to prison If I heard of someone running this type of operation

I would turn them into the police personally They take the fun out of recreational drugs andreplace it with danger I do not intend this book to be used for making drugs, but maybe thechemists who are producing drugs will use this material to make better, healthier drugs

Most drugs are made from or with highly toxic or poisonous chemicals, if used improperlythey can cause disease, cancer, or immediate death Even the most simple of chemical reactionsare not to be taken lightly or unprofessionally Go to a college or some other type of professionallaboratory and ask if they will show you around; seven times out of ten they will give you atour Look over their equipment; notice the cleanliness of even the floor Look at the chemiststhemselves; see how serious and professional they act This is how your laboratory should look

2 RECREATIONAL DRUGS

As I said above, I do not want to have this book used for the illicit manufacture of drugs, but

if you are going to, or have been making drugs, then I have accomplished everything if I havetaught you how to make them right Many analogs of some drugs can be legal to produce, butthis does not mean that you can skimp on purification or other important operations described

in the formulas I do not approve of "kitchen crank" or other high speed, slipshod operations.This is how drugs get much of their bad reputation If drugs were not illegal, we could buy themfrom major pharmaceutical manufacturers and eliminate much of the bad dope that is beingabused today Unfortunately, we have given up many of our rights over the years, due to ignorant,hypocritical assholes in positions of power, and we are forced to make these drugs ourselves So

we must act as though we are the major pharmaceutical manufacturers and we need to force selves to abide by the same rigid rules that the Food and Drug Administration imposes upon them.Besides, the recreational drug abusers are paying good money, they deserve good drugs, after allthey're only trying to have a good time

our-Laboratories, like any other investment, require a certain amount of capital to start and operate.Spend the necessary cash to buy the proper equipment to do the procedures required Faultyequipment (not to mention insufficient knowledge) can cause fires, explosions, asphyxiation, andmany other hazards You can have one hell of a nice laboratory for the price of a funeral thesedays Also hospitals are in excess of $150 a day if you are not in intensive care or requiring specialservices $150 a day can operate even the most elaborate of laboratories Therefore, if you have

to beg, borrow, or steal to obtain a functional laboratory, then do so Is three to five thousanddollars too much to spend on a lab that can easily produce a quarter of a million dollars worth

of THC every week? It takes money to make money, but very few, if any, investments can payoff as well as an underground laboratory run by competent chemists

Although this book is written in easy to understand language and the formulas have beengreatly simplified, they should not be attempted by the chemically incompetent The chemicallyincompetent are those who never took, passed or remember freshman college level chemistry Isuppose that if you were an A student in high school chemistry, you may be smart enough tounderstand what you're doing with these formulas If you do not fall into these categories, thenstop reading this book right now You have no business in an organic laboratory

Most of the organic compounds listed in this book are highly flammable and have irritating,toxic, and/or poisonous vapors Many of the reactions in the following formulas are potentiallyviolent and if performed improperly will become violent If people understand why atoms andmolecules behave the way they do under all conditions, they will know how much reagents touse, how fast to add the reagents, what kinds of poisonous byproducts may be formed and whatdangers are involved It is not enough for me to tell you that heating this and that, then reducing

it makes a drug This is unprofessional and dangerous I want you to understand why you do

what is required of you to complete a given formula, and a basic knowledge of chemistry is adefinite prerequisite If you forgot, or never knew the meaning of enthalopy, chemical bonding(ionic, polar, non-polar, bond energies), elemental and molecular properties, proton donating,dynamic equilibrium, entropy, reaction mechanism, orbital, phase, redox, pH, photon, rate ofreaction, atomic mass, reduction, etc., etc., then you must put down this book and read one ormore of the following references until you completely understand what is going on while youare performing these or any other formulas or reactions:

NEW ORGANIC CHEMISTR Y, by H.L Keys

PRACTICAL ORGANIC CHEMISTRY, by Vogel

Preface 3

ORGANIC CHEMISTRY, by Butler & Berlin

PRINCIPLES OF ORGANIC CHEMISTRY, by Geissman

C.R.C HANDBOOK OF LABORATORY SAFETY

BASIC PRINCIPLES OF ORGANIC CHEMISTR Y, by Roberts & Caserio

PRINCIPLES OF MEDICINAL CHEMISTRY, by Foye

This is a short list Hundreds of good chemistry books are available at any library or bookstore It should only take a week or two to read and the importance of this cannot be overstressed.Try to find one that has questions at the end of each chapter, so you can see if you can answerthe questions If you can, great, go on to the next chapter; if not, read it again, Reading is nothingwithout understanding

These books will teach you how to solve and balance chemical equations, find molecularweights, how to double or triple the scale of your formula (multiplying the given formula by two

or three rarely works as rates of reaction and dynamic equilibrium change much more differently

as the mass of reagents and precursors are increased) and other necessary information I wouldlike to have included this information but it would take several decades to do so and the finishedbook would be longer than four holy bibles combined With so many good chemistry booksavailable, it would be impractical for me to- do this

Most of you will not heed my advice to read some chemistry literature until after you waste

$800 worth of chemicals on one small mistake or maybe it will take a laboratory explosion toexplain how important some simple chemistry book can be

4 RECREA T1ONAL DRUGS

SAFETY

Before commencing any procedures in organic chemistry, you must become familiar with thesafety, hazards, apparatus and methods described here in this book and in the referred reading.Those of you who think "I don't need to learn all this preliminary bullshit, because the formula

is in easy to understand language" are wrong — dead wrong

It is true I have reworded the formulas so that the average high school student can understand

and complete the operation easily However, I do not have time to warn the unknowing and

incompetent every time a potential hazard is encountered, as most every chemical has dangerousproperties Ethyl ether, as an example, has more BTU's than dynamite and is much more easilyignited I will not waste time or paper to describe the properties or dangers of every chemical

encountered in every formula It is the duty of any chemist, amateur or professional, to learn these

properties Know what you're dealing with at all times, under all conditions I have taken muchtime compiling a superb glossary of most every chemical, operation and apparatus encountered

in this book If you find something I have not listed in the glossary, or if you use a formula not

listed in this book, do not assume it to be unimportant Look it up in the Merck Index and

remember its properties

Anyone who has been asphyxiated or even seen some large third degree bums caused by

chemicals or heat, will be able to relate to the rigid safety measures I will impose on you in thischapter

FORES

A small fire extinguisher is cheap and very effective It should be purchased and located in

an accessible position before any chemistry is undertaken I have known underground chemists

that thought it more important to spend $40 on a glass flask than to spend that same $40 on

a simple little fire extinguisher One such chemist experienced a small fire that escalated into amassive inferno, destroying hundreds of dollars worth of glassware, chemicals, books andthousands of dollars of property A small fire extinguisher would have stopped the small fire before

it became out of control, even for the local fire department Also, all fire calls must be investigated

by the fire marshall, who would undoubtedly call the authorities when discovering that the cause

of the fire was a drug laboratory The result, an easy bust

Other fire prevention items include:

1 A fire blanket This is useful for tossing onto table tops and floor fires Even more important,

it can be used to wrap around yourself or a helper who has caught fire These blankets can

be made easily and cheaply by going to fabric or upholstery stores and purchasing a generous

Safety 5

length of non-flammable material It must be thick enough to keep air from passing through

it Ask the sales person what types of material are flame resistant and how much they cost.You should also ask how much they charge to sew an apron for you, as they are extremelyprotective in acid spills, fires, explosions, etc It should be known that some chemicals (i.e.tetranitromethane, nitromethane, concentrated hydrogen peroxide, etc.) are very strongoxidizers, allowing them to burn vigorously without oxygen So, not only can they be used

in a monopropellant rocket motor, they can make fires that are difficult to put out and theymay explode violently when exposed to impurities or the wrong chemicals, metals, etc.That's right, folks, no spark or flame necessary for combustion If you should use a chemicallabeled "oxidizer" be extra careful with storage and handling

2 Sand bucket Flammable liquids tend to spread out when spilled, and when spread out these

liquids give off much more volatile, flammable fumes increasing the hazard of fire greatly

If confronted with this type of fire, resist the urge to fight these flames with water, as thiswill just make the fire bigger by adding more volume to the liquid under the flames Aswith any fire, remain cool and collected, quickly go over to the five gallon bucket full ofsand (that you conveniently stashed by your work bench) and toss heaps of sand directly

onto the fire and its fuel If the fire still burns after most of the liquid has been soaked up,

smother the flames with your blanket or give them a quick burst with your extinguisher.Extinguishers sometimes have so much pressure that they blow and spatter the fire all overthe place before putting it out, so when large quantities of flammable liquids are spilled andburning, use sand first, it makes clean-up easier

3 Fire extinguishers Never use a carbon tetrachloride extinguisher, as these cause phosgene

formations Always use a COi (carbon dioxide) extinguisher A box of baking soda can beused to smother small fires Fires inside a flask or beaker can be smothered by coveringthe mouth of the container with a nonflammable item, i.e., a glass plate

If your clothes are on fire do not run I know this sounds stupid, but the faster you move the

faster and hotter your clothes burn Walk to your fire blanket or a nearby shower If you weretoo stupid to get a blanket and there is no nearby shower, try rolling on the floor and dumpingsand or baking soda on yourself If you have received a severe burn, do not touch or anoint itwith anything, get medical attention at once

Two important rules that are to be observed without exception are:

1 Eye protection must be worn at all times Safety goggles are the ultimate; safety glasses withside shields are acceptable; prescription glasses are better than nothing, but should be wornwith goggles; hard and soft contact lenses are useless

2 Never work without someone near enough to hear a cry for help This person should makevisual checks on you frequently to make sure you are not gassed or asphyxiated

Here are a few minor rules to practice:

1 Never taste any compound until the formula requires you to do so Drug testing should betried on animals first

2 When smelling a chemical or compound, never inhale, sniff from a fair distance

3 Avoid contact of chemicals with your skin Playtex type gloves are cheap and effective Ifcontact occurs, wash immediately

4 Never heat any flask or apparatus that is not open to the atmosphere (have an outlet for

pressure to escape) unless properly equipped (see reductions chapter)

6 RECREATIONAL DRUGS

5 Use water bath, steam bath, heating mantle, or hot plate when heating or distilling volatile,inflammable solvents (inflammable means BOOM!) Never use a bunsen burner and turn

off all pilot lights

6 Never smoke in the lab Vapors collect and hang around long after escaping from bottlesand flasks

What to do if you are burned by:

a Acids Wash immediately with lots of cold water, then with diluted sodium bicarbonate

(2 or 3 tablespoons of baking soda in one cup of water) Rinse again with water andseek medical attention if irritation persists

b Alkalis, bases Wash in turn with water and vinegar Diluted acetic acid may be used

in place of vinegar If the burn is severe or irritating, see a doctor

c Bromine Same procedure as acid burn.

d Phenol and like substances Remove with a solvent that is not very toxic (ethanol or

methanol) Then rinse with very diluted bromine solution (one teaspoon per quart ofwater) in glycerol

e Phosphorus Wash immediately with sodium carbonate solution followed by warm 1%

copper sulphate, then remove any copper coated phosphorus with forceps and/or gentlyrunning water

Let's say you thought that goggles were a waste of time and a real pain in the ass So youtook them off, or never even purchased them Now you experience caustic spurting (verycommon), or maybe the stopper blows out of your flask and you have reagents in your eyes.Chances are two to one that you are now permanently blind

What to do if reagents get in your eyes:

a Acids Wash with running water or wash bottle, clean water from beaker, or anything

with clean water, and do it fast Follow with diluted (1 to 2% sodium bicarbonate to 98%

water) baking soda solution Then drop several drops of castor oil into eye(s)

b Alkalis Wash with water, then with dilute boric acid solution, then a drop of oil.

c Glass shards in eye Unless this is easily removed with forceps, do not attempt to dislodge;

hold eye open, no blinking (yes, this takes great will power) and absolutely no rubbinguntil a doctor can remove fragment(s)

In case of asphyxiation, remove victim to fresh air first, and remove restrictive clothing aroundneck and chest Perform artificial respiration and send for doctor If gassed while working alone,you will pass out and continue to be gassed until death

Equipment, Technique and Reagents 7

EQUIPMENT, TECHNIQUE,

AND REAGENTS

Glassware A typical set of glassware with standard taper ground joints like those shown in

Figure 1.1 would be employed in an undergrad course The joints permit you to assembleapparatus quickly and securely, but they must also be greased carefully (do not let the vaselinesqueeze down into reaction vessel), and they are acceptable only with joints that have the sameexact taper Never use 24/40 joints with 19/22 or 14/20 or vice versa Never use ground glassjoints with formulas requiring diazomethane; clear seal joints are available at a small extra charge

Never perform a reaction without greasing glass ground joints

Rubber stoppers may be used if you cannot afford ground glass jointed glassware Rubberstoppers may be used in conjunction with ground glass joints Make sure your rubber stoppersfit properly and lightly grease inside and outside with vaseline Bore holes in stoppers carefullyand size them to fit apparatus snug

Cork stoppers can react with or contaminate certain chemicals and should not be used

Other glassware necessary are as follows:

Erlenmeyer flasks and beakers These are fairly expensive and may be replaced with heat proof

pitchers found on coffee makers Corning and several other companies make many different types

of heat proof glassware that can be picked up at yard sales dirt cheap and used effectively in thelaboratory Remember, even the best glass can be broken by a rapid change in temperature Sep-aratory and addition (dropping) funnels are sometimes the same piece used in either role In somereactions they are a must They have a valve at one end and can be stoppered at the other endand the entire funnel, even the valve, is made of glass

Filtration and pouring funnels These should be glass or stainless steel unless working with very

"mild" compounds, e.g., H20; then plastic and aluminum are acceptable Buchner funnels and theirsubstitute will be discussed under filtration in the methods chapter

Graduated cylinders These are necessary and inexpensive You should have a small size for

measuring small amounts accurately (25 ml) and a large size for measuring large quantities rapidly(250 ml)

Capillary tubes These are made from glass pipets by heating a pipet or glass tubing and pulling

them in two when the glass has reached a workable temperature These items are inexpensive

and practice makes perfect

Thermometers A high quality thermometer is only about $8 It is best to purchase two — one

for high temps and the other for low temps Make certain it is for measuring degrees in centigrade

as this is what all formulas require, unless specified differently Candy, meat and other types ofthermometers will not fit your apparatus, are not accurate enough for most reactions and are

unacceptable

8 RECREA TIONAL DRUGS

Stirring Stirring is usually unnecessary in reactions that require boiling as the turbulence of

boiling is sufficient In other reactions a stirring device shown in Figure 1.1 cannot be beat Ifthe reaction can be carried out in a beaker, then an eggbeater can be used if set up exactly asshown on the work bench diagram Variable speed eggbeater type mixers are powerful, fast,

cheap, plentiful and with a little ingenuity can easily be adapted to any stirring device, but theymust be housed in a vapor proof box and must be mounted securely Low amperage, sparkless,stirring motors can be bought from an electrical repair shop dirt cheap Make sure they aresparkless or mount them inside a vapor box, like the eggbeater Every lab should have at leasttwo mixing devices, in case one mixer breaks or in case two different compounds need to be stirred

at the same time Low amperage motors should be available for those formulas that require longperiods of stirring Magnetic stirring devices can be bought or built, but I feel they are weak,troublesome, expensive and inferior to a good mechanical setup

Heating There are three different sources for heating and your lab should have all three.

Bunsen burners These are of very limited use, as most reactions require flammable substances.

Their purpose is mainly for gkss work, generating and super heating steam (see work benchdiagram for safe usage)

Steam heat It is very easy to produce and can be used safely for so many things: steam

distillations, steam cleaning, creating a vacuum, etc No lab should be without it Make sure thatsteam does not get into anhydrous or dry reactions

Electric heating elements These should also be available in your lab They are sometimes the

only heating device capable of producing higher temperatures

Heating mantles These are state of the art devices and are worth the cost Show the plans from

the work bench diagrams to someone electrically inclined A good electrician can make you one

of these in a matter of minutes and he should have all the parts laying around his shop He should

charge just a fraction of the price of a heating mantle (Note: Make sure he knows that the element

he made will be exposed to flammable vapors.)

Heating plates Even if you have a good heating mantle you should get a heating plate These

are made from electric fry pans if done as shown If you are unsure of what wire to use, ask

someone who knows Fry pans are usually good for developing 400°F (205°C) This is sufficientfor most distillations, refluxing, and drying

JOINTWARE

three way adapter

water

condenser

claisen adapter

Equipment, Technique and Reagents 9

separation

funnel

three neck flask stopper

JOINTWARE (Continued)

stirring device

inlet adapter

capillary with fine outlet

distilling column

10 RECREATIONAL DRUGS

CRYSTALLIZATION

The solid product is seldom pure when obtained from a chemical reaction, being contaminatedwith various impurities, reagents and byproducts For purification, the process of crystallization,sometimes called recrystallization, is generally employed When dealing with large quantityformulas, the utmost care should be taken to obtain the maximum yield of a pure crystallizedcompound

Crystallization by Cooling The ideal solvent is one in which the compound to be obtained in

pure crystalline form is insoluble at cold temperatures, but readily soluble at hot temperatures.Also the impurities should either be insoluble or else very soluble and filtered accordingly toremove In real life operations, this perfect solvent cannot always be found, so the nearestapproach to it should be selected

The solvents most commonly employed are: water, ethyl and methyl alcohol, ether, benzene,petroleum ether, acetone, glacial acetic acid; also two or three solvents may be mixed to get thedesired effect as described later If you still cannot dissolve the compound, try some of these:chloroform, carbon disulfide, carbon tetrachloride, ethyl acetate, pyridine, hydrochloric acid,sulfuric acid (acids are usually diluted first), nitrobenzene, aniline, phenol, dioxan, ethylenedichloride, di, tri, tetrachloroethylene, tetrachloroethane, dichloroethyl ether, cyclohexane,cyclohexanol, tetralin, decalin, triacetin, ethylene glycol and its esters and ethers, butyl alcohol,diacetone alcohol, ethyl lactate, isopropyl ether, etc

If unsure of what solvent to use, look in the Merck Index or in a chemistry handbook This

may save you the time and expense of testing for the best solvent

Choosing a Solvent In order to select a suitable solvent, place small quantities, (50 to 100 mg)

of product into several test tubes and treat with a few drops of single solvents of the above class

If the product dissolves easily in the cold upon shaking or if it does not dissolve appreciably onboiling, the solvent in question may be regarded as unsuitable Where the product 01 substancedissolves on heating or boiling, and separates out again on cooling, the solvent used is suitable;make sure that you choose the solvent that gives good crystals in the greatest abundance At times,crystallization will not take place due to cooling or even supercooling; in such a case, the side

of the glass container should be rubbed with a glass rod, and/or "seeded" by the addition of avery small amount of crude product, since such operations often induce crystallization Withsubstances which are sparingly soluble in the common solvents, solvents of high boiling pointssuch as toluene, nitrobenzene, etc., should be used

Where no single solvent is found suitable, a mixture of two mixable solvents, one of whichthe product is soluble and the other insoluble, may be used The substance is dissolved in a smallquantity of the solvent that has the strongest dissolving power, then the solvent that does notdissolve the product, is added until complete crystallization occurs This process can be carried

Crystallization 11

out with or without heat Let me use an example You just dissolved a few grams of nitrostyrene

in a small (always use a small amount of solvent if possible) quantity of boiling ethanol and uponcooling in a freezer no crystals appear Next, you try "seeding" and another hour in the freezer,but still no luck By testing small amounts of the styrene with different solvents you find somethingthat will not dissolve it, so you add this solvent slowly to the hot or cold styrene solution andthe product crystallizes, if not you must now take much time to evaporate both solvents Needless

to say that this does little purification and may take days Evaporation is greatly speeded up ifdone under vacuum conditions

To Prepare Solutions If considerable heating is necessary, a reflux condenser should be

em-ployed to avoid loss of solvent Where the resulting solution does not require filtration, a conicalflask should always be used During any heating, the contents of the vessel needs to be frequentlyshaken or stirred, since the crystals melt to a heavy oil settling on the bottom of the vessel makingthe vessel liable to crack

In preparing the solution, an excessive amount need not be employed at first; successive smallquantities should be added to the boiling or near boiling solution until the substance just com-pletely dissolves, or until nothing but impurities remain undissolved With substances of lowmelting point, care should be taken that concentrated solutions from which the substance com-mences to separate at temperatures above its melting point are not used,

Crystallization by Evaporation This method is employed when the substance is so easily soluble

in all solvents (hot or cold), that it will only crystallize after, partial or complete evaporation Ifcomplete evaporation must be employed, impurities will remain So, if possible, filter off themother liquor (solvent), as this is where the dissolved impurities will be If you should need toheat the product with an effective solvent until thoroughly dissolved, pour through filter paper

to remove solid impurities

The type of vessel employed depends on volatility of the solvent; obviously the conical flaskalready recommended for "crystallization by cooling" is not suitable for spontaneous evaporation,while a beaker or shallow dish is When the latter type of vessel is used, "crusts" often form onthe sides above the surface of the liquid Such crusts seldom consist of pure substance so theyshould be removed carefully with a spatula or spoon before attempting to filter off the crystals.Another method that can be used, if the above methods fail, is to dissolve the substance insome solvent, then add a second solvent mixable with the first solvent, but in which the substance

is not soluble or sparingly soluble The first solvent is then gradually removed and the substancecrystallizes back out If the first solvent is more volatile than the second, it can be evaporatedout of the solution leaving the non-soluble solvent behind to crystallize the substance If the first(dissolving) solution is not as volatile as the second solution, place the solution in a desiccatorover some substance which absorbs the first solvent but not the second; in this way water may

be removed from a water-alcohol solution by caustic potash or quicklime

If a substance can only be crystallized by total evaporation, it can usually be purified by ation first

distill-FILTRATION

Filtration by means of suction is employed, when possible, as this gives a more rapid andcomplete separation of mother liquid from substance Most any funnel can be made to work if

12 RECREA TTONAL DR UGS

equipped with a platform on which the filter paper can lay Such a platform can be made from

a small ceramic plate with many small holes drilled through it or wire mesh As long as theplatform does not react with your substance, it should be acceptable Buchner funnels (see Figure1) come with perforated discs and are inexpensive

clamp

to vacuum source ring

stand

Figure 1

Some things to remember during vacuum (suction) filtration are: the funnel tip should be below

the vacuum source outlet, cut your filter paper to fit the funnel platform exactly, in other words,

do not let the paper rest on the sides of your funnel

Hot Filtration A device such as the one pictured in Figure 3 is easy to make out of tubing

and is very effective It will be required when substances crystallize before passing through thefilter paper while filtering out non-soluble impurities

copper, lead or aluminum tubing

Figure 3

steam outlet

Crystallization 13

Cold Filtration These devices (Figure 2) can be made by cutting a one gallon milk jug in half

and sealing the bottom to fit your funnel with silicon, grease your funnel lightly with Crisco orbutter so it can be removed after the silicon has set up For a list of freezing mixtures see coolingsection

PORE SIZES FOR GLASS OR PAPER FILTERS

mercury filtersextraction of medium grain materialfine gas and mercury filters

extraction of fine grain materialanalytical and preparative work of the finest precipitatesbacteriological filtration

Cooling Some formulas call for external cooling of the reaction These temperatures should

be followed exactly or the product intended may evolve into something completely different Toaid you in cooling, I have listed the following substances to be mixed and the temperaturereductions created by them If carried out in an insulated container these mixtures will hold amore even temperature for a much longer period Those little Playmate lunch boxes make perfectinsulated containers

Mixture of substances

250 calcium chloride cryst + 100 aq

8 sodium sulphate + 5 cone HC1

25 amm chloride + 100 ice

45 amm nitrate + 100 ice

50 cone HC1 + 100 ice

33 sodium chloride + 100 ice

1 pot thiocyanate + 1 aq

14 RECREATIONAL DRUGS

If you do not understand any of the above abbreviations or if you have no idea which of thesechemicals are hazardous, then you need to go back and read some type of basic chemistry beforeattempting these simple cooling mixtures

Chromatography \ 5

CHROMATOGRAPHY

Vapor Phase Chromatography This is accomplished by constructing or buying complicated and

expensive equipment Although this method is very effective, it is superseded by the simple,inexpensive and effective column chromatography

Thin Layer Chromatography Thin layer chromatography is primarily a tool for small qualitive

analysis (deciding which solvents elute which substances, etc.) A microscopic amount of sample

is applied at one end of a small plate covered on one side with a thin absorbent coating The

plate is then dipped into a shallow pool of solvent which rises on the coated layer, permitting

the compounds of the sample to move with the solvent to differing heights The individualcomponents can then be detected as separate spots along the plate Unfortunately this process canonly be scaled up to do several grams at a time, again making column chromatography thechampion of chromatography

If, however, you wish to use thin layer, consult your local

library on methods I chose not to go into depth on thin layer

because it is so inferior to column style

Column Chromatography The main idea here is to dissolve

your mixture and put it on the adsorbent, at the top of the

column Then you wash the mixture down the column using

at least one eluent (solvent), perhaps more The compounds

of your mixture are carried along by the solvents and washed

out of the column at different rates and collected into separate

flasks Why do you want to do this? Let us say you have a

substance that needs to be purified, but it cannot be distilled

because it decomposes at a low temperature, or you wish to

extract one of many mixable liquid substances that have been

mixed together, etc A column chromatography can separate,

purify and extract

Preparing The Column Alumina or silica.gel is supported

by glass (see Figure 7) with a valve to control the flow of

eluent Right above this valve place a fritted glass disc or a

wad of glass wool or cotton to keep everything from falling

out Do not use too much, and do not pack it too tightly, or

solvent sand

sand

product

ruining the column Add the adsorbent slowly Use about 25 g of adsorbent for every 1 g of

mixture you want to separate When the alumina settles, add another 1 cm of sand to the top

During the entire procedure the level of the eluent must be higher than any solid material placed

in the column,

Now you may open the valve until there is a little over 1 cm of solvent above the top layer

of sand If there are any cracks or air bubbles in the adsorbent, dump everything and start over.Dissolve the mixture (your substance) in the same solvent you are going to put through thecolumn, keeping the amount as small as possible (this is called the analyate) You should be usingthe least polar solvent that will dissolve your substance Now you may add the analyate very

carefully; do not disturb the sand Open the valve until the level of the column is the same as

it was before you added the analyate (1 cm above the sand) At no time let the solvent level

drop below the sand! Add the required eluent (solvent) to the column, not disturbing the sand.Open the valve to slowly let the eluent run through the column until the first compound comesout Collect the different compounds in different flasks At no time let the solvent drop belowthe top of the sand! If necessary, stop the flow, add more eluent, and start the flow again

Should the compounds be colored, you can watch them travel down the column and separate,changing collection flasks as the colors change If your compound is clear then you will have

to use one of the following steps:

1 Occasionally let one or two drops of eluent fall onto a microscope slide Evaporate thesolvent and see if there are any properties of the compound that should be coming through,such as crystal shapes, tastes, smells, viscosities if oil, etc

2 Occasionally use several drops to spot, develop, and visualize a thin layer chromatographyplate Although thin layer is very similar to column, you should read up on it as I do nothave time to go into the complete operation

If you find the eluents are taking an excessive amount of time to wash down the compounds,then switch to the next most polar solvent If you had two compounds and one of them is alreadycollected, then go ahead and get some really polar solvent and get that last compound pronto

List of solvents arranged in order of increasing polarity Note: This is a very small list of many

solvents

(Least polar)

(Most polar)

petroleum ethercyclohexanetoluenechloroform

acetone

ethanolmethanol

2 Place the condenser upright on flask and clamp.

3 Adjust your heat source so that the vapors travel no further than halfway up the condenser.Add another condenser if your formula requires a specific temperature and you experiencevapor travel higher than halfway at that temperature Also use drying tube with anhydrous

18 RECREA TIONAL DR VGS

DISTILLATION

There are four types of distillation processes; find the one that suits your needs and record ormemorize the operation

Class 1: Simple distillation Separating liquids that boil below 150°C at one atmosphere (1

atm) from non-volatile impurities or another liquid boiling at least 25°C higher than the firstliquid Note: the liquids to be distilled must be mixable with each other If they are not then theywould form separable layers, which you separate much more easily with a separatory funnel

Class 2: Vacuum distillation Separating liquids that boil above 150°C at 1 atm from

non-volatile impurities or another non-volatile liquid that boils at least 25°C higher than the first liquid

Boiling points can be found in the Merck Index.

Class 3: Fractional distillation Separating mixable liquid mixtures that boil at less than 25°C

from each other at 1 atm

Class 4: Steam distillations Separating or isolating tars, oils, and other liquid compounds

insoluble or slightly soluble, in water at all temperatures These compounds do not have to beliquids at room temperature

Now that you know which class you need, I will discuss each one in great detail, but remember,you should know how to do a Class 1 distillation before attempting a Class 2, and so forth

CLASS 1: SIMPLE DISTILLATION RULES

1 Never use a bunsen burner on compounds that boil below 70°C, or on flammablesubstances

2 Make all ground glass joints and or stoppers fit tight and secure

3 Do not fill the distilling flask more than half full

4 Always use a boiling stone, but never add a stone to any hot substance or you will wearthe hot substance

5 Place your thermometer bulb just below the vapor outlet If the thermometer does not havedrops of condensation dripping off of the bulb then the reading is not correct

6 Use plenty of clamps to secure your apparatus tightly

7 Always allow a way to relieve pressure at the receiving flask end of the setup, or the distillingflask will surely explode

Distillation 19

8 Start your heat slowly until gentle boiling begins and liquid starts to drip into the receivingflask at about ten drops per minute You may have to increase the heat to keep materialcoming over

9 Always keep cold water running through the condenser, in the bottom and out the top (seeFigure 12)

10 When temperatures change rapidly or drastically, this usually indicates that the compoundcoming over has changed also; you should change the receiving flask with a clean emptyflask to keep your products separated

Figure 11

water out

air condenser for use on liquids that boil over 160°C

Figure 12

to vacuum source

if required — must be left open

if not required

Figure 10 for high B.P.

This is for ing air condener

attach-to vacuum source

Figures 8, 9, 10, 11, and 12

20 RECREATIONAL DRUGS

CLASS 2: VACUUM DISTILLATION RULES

1 Learn all the rules on Class 1 distillation.

2 The thermometer can be replaced with an inlet tube If your flask has the provisions forboth a thermometer and an inlet tube, then by all means also leave the thermometer in thereaction The inlet tube should always be used to prevent the bad bumping that goes alongwith vacuum distillations Boiling stones are useless

3 Inlet tubes should have capillaries so small that the vacuum is not reduced An inert gas

like nitrogen should be introduced through the inlet tube if the compounds decompose inair

4 Control of the heating is very important! After applying the vacuum, increase the heat very

8 A Claisen adapter can be added to allow use of both inlet tube and thermometer If you

must decide between the two then pick the inlet tube

vacuum / adjusting

1 valve

water jacket condenser manometer

column

Figure 13 and 14

Distillation 21

CLASS 3: FRACTIONAL DISTILLATION RULES

1 Read all the rules on Class 1 distillations

2 Do not confuse the condenser with the column The column is wider, and has glassprojections at the bottom to hold up the packing (see Figure 14)

3 Do not run water through the column jacket

4 Occasionally, the column is used without any column packing

5 Do not break off the projections that support the column packing

6 If necessary, push a small wad of heavy metal wool (stainless steel, etc.) down to the bottom

of the column to support small packing particles Sometimes this wool is the entire packing

7 Make sure that the packing will not fall into your distillation flask,

8 Lots of liquid will be held up on your packing, make sure that you have enough compound

to start with, or it will all be lost in the packing

9 Do not distill with too much liquid Never fill the flask more than three fourths full

10 For maximum yields, a chaser solvent should be used to push the compound that is leftbehind in the column on over into the condenser

Special Note: Azeotropes

Certain liquids cannot be completely separated even by fractional distillation with the bestequipment These are the dreaded azeotropes, mixtures with a constant boiling point

One common azeotrope is ethyl alcohol 96% water 4% This combination can be boiled todryness at one constant temperature I cannot go into all the azeotropes you may run into during

drug manufacture So, before you attempt any formula, you must go to a science library and

research all of the chemicals, solvents, reagents, etc., that are used in that particular formula and

learn what can and cannot be used with what Look in Chemical Abstracts, the Merck Index,

or one of the many other fine reference books available

For an example, let's say you want to chase some ethyl alcohol through your column packing.You notice that the boiling point of water is high enough to push or chase the lower boiling ethylalcohol out of the column Instead, they formed an azeotrope

If an azeotrope boils off first, it is a minimum boiling azeotrope The remaining liquids willnot distill until all the azeotrope is gone If the other liquids come over first, followed by theazeotrope, then you have a maximum boiling azeotrope

CLASS 4: STEAM DISTILLATION RULES

1 There are two ways of generating steam for this distillation:

A Leading steam directly into the system This is a little more complicated and requires

a water trap to keep excessive water from ruining the distillation (see Figure 15)

22 RECREA TIONAL DRUGS

rubber tubing to connect glass tubing

\

Devices To Superheat Steam

water condenser

to vacuum

condenser

heating mantle

or hot plate

valve

This is to make pressure equal in funnel

Figure 16

2 Read all the rules on Class 1 distillation.

3 Use at least three times as much water as sample Do not fill the flask much more thanhalf full

4 Keep adding more hot water as needed As the water boils and turns to steam, it leavesthe flask, carrying sample

5 The sample or product is still coming over if you see two layers or cloudy solution in yourreceiving flask

thermometer

steam

between flame and tubing

flame bunsen burner

Figure 17 and IS

Distillation 23

6 If the solution is clear then you should add a little salt to a small sample of the solution

If two layers form, then you need to keep on distilling

7 To find out which layer is water or product, add a little water and watch carefully Thewater you added will go to the water layer

8 Do a back extractions with an immiscible solvent to get most of the product from the waterlayer

THE SOXHLET EXTRACTION

This apparatus is not totally necessary when called for in a formula,

but for the modest price of the apparatus, or the little bit of work with

which a homemade unit can be constructed, it is worth carrying out the

formula with such a device Also, yields are improved considerably,

sometimes paying for the apparatus with the first formula completed

The principle is basically the same as any coffee pot; a paper thimble

is filled with the substance to be extracted (F) and a loose plug of cotton

is placed (E) over the top The Soxhlet apparatus is attached to a flask

containing the proper solvent (if the solvent is not given in the formula,

then usually you must find a solvent in that either the desired substance

or the impurities are insoluble in) Attach a condenser to the Soxhlet

tube (B) The solvent is boiled causing vapor to rise and pass through

the holes (C) into the condenser where it is turned back into liquid The

liquid drops down into the thimble and solvent When the solvent level

exceeds the top of the riser tube (D) the solvent overflows back into

the boiling flask (G) and the process is recycled or continuous

You should use a minimum amount of solvent, and if necessary add

more through the condenser (do not use too much and do not let the

flask (G) become dry at any time) When the extraction is complete,

dismantle the apparatus and crystallize the substance from the solution

in the flask, or separate the resulting oil, etc

This is the most efficient way to get myristicin from nutmeg

EXTRACTING AND WASHING

Some people find these two important operations complex and confusing, when they are

actually quite simple You extract good substance from impure mixtures You wash impurities

from good material

Solid — Liquid Extracting This is not done too often, but if you have ever made tea or coffee

you should be able to do this, as it is basically the same thing

Liquid — Liquid Extracting This requires a separatory funnel and two liquids (solutions) that must be insoluble in each other The liquids must form two layers in the funnel or washing or

24 RECREATIONAL DRUGS

extracting cannot be performed Solids (crystals, etc.) need to be dissolved in a solvent, and thatsolvent must be insoluble in the extracting or washing liquid Never throw away any layer untilyou are sure that it does not contain product

Using The Funnel Add the liquid to be extracted or washed to your funnel; if you forgot to

close the valve your liquid is now on your shoes Add the extractor or washer carefully to themixture Install the funnel stopper and invert so that the stem points to the roof; make sure one

of your hands is holding the stopper securely inward Most of these liquids fizz when mixed withthe extractor, creating pressures that must be bled off through the valve as follows Swirl or shakeonce very gently while still pointing the stem at the roof, then open the valve to bleed or "burp"the pressure Close the valve and shake twice, then burp the funnel Keep increasing the shakingbetween burps until you can shake the living hell out of the mixture for long periods, as this isthe type of agitation necessary to extract or wash

DRYING

Remember the ethyl alcohol — water azeotrope? You might be thinking: If I cannot distillthe water out and I want my alcohol anhydrous (dry), because the water will kill my yield, whatshould I do? You need to dry Sometimes you will have to dry reagents, sometimes solvents, andsometimes the products themselves

Baths Baths can dry many solid substances that do not decompose under heat Some substances

can take more heat than others so a thermometer must be used along with the knowledge of howmuch heat can be safely used without destroying the product, or changing it into a differentsubstance The types of baths are many: water, air, toluene, sand, oil, and graphite, but they allhave the same general rules Hot plates and heating mantles must follow these rules also

1 Always protect the substance you are drying from the water in the atmosphere by fitting

a drying tube into the glassware that is holding your substance The drying tube should befilled with a suitable drying agent

2 If using a liquid, never allow it to boil

3 Never use excessive heat for drying I have heard of nitro propene burning faster thangunpowder due to excessive heat Personally, I feel this could have been caused by a nearbypilot light that was left burning

Solids can also be dried at room temperature on filter paper or porous tile You should protectthe substance from dirt and dust by covering with filter paper or a funnel A vacuum desiccatorwill greatly speed up the drying process, and should be used on products that are destroyed bythe small amount of water in the atmosphere A vacuum desiccator is shown in Figure 4

Drying of Liquids Liquids are usually dried by filtering through or mixing with a solid

dehydrating agent The most common solid drying agents are: calcium chloride, sodiumhydroxide, caustic potash, anhydrous sodium sulphate, anhydrous potassium carbonate,anhydrous cupric sulphate, phosphorus pentoxide, and metallic sodium Now for the bad news,

it is essential that the drying agent have no action on the liquid or any substance that may be

in the liquid Great care should be used in the choice of a drying agent, and much research may

be required If you do not find the necessary information call a chemist or some one who knows

I will mention a few rules

Distillation 25

1 Never use calcium chloride to dry alcohols or amines

2 Never use caustic potash or caustic soda to dry acids, phenols, esters, certain halides, etc

3 Always use a very small amount of drying agent, otherwise you will lose product by

excessive absorption It is better to use several small amounts than to use one large excessiveamount A useful agent called Blue Drierite can be mixed with the cheaper White Drierite

and visually inspected to determine if its absorbing powers are used up Blue Drierite turnspink when it has no more absorbent power If you use Blue Drierite directly, you take achance of contaminating your product with a cobalt, as it was made for use in drying tubes

(see Figure 8)

4 To dry a moist solid it is often convenient to dissolve it in ether and dry this ethereal solutionwith the proper drying agent Evaporate to retrieve the solid

MELTING POINTS

Melting points are important for determining the purity of solid products

A small amount of sample is packed into the closed end of a capillary tube

with a wire or small glass rod It is then attached to a thermometer, keeping

the sample next to the bulb as shown (see Figure 19) Next submerge into

oil filled tube, keeping setup in the middle of tube (do not touch the sides

or bottom) Watch for temperature at which solid sample melts

REAGENTS

I cannot give you directions to prepare every possible strength of every

known reagent, but I can give you enough examples to figure out how to

prepare any percentage or strength you might need to prepare No matter

what you are making, the rules below are to be followed

1 Only the purest chemicals should be used unless another grade is

4 Do not pipette strong acids or alkalis by mouth Use a rubber bulb or

an adjustable vacuum source

5 Hot and cold liquids should be allowed to come to room temperature

before measurement

6 Only distilled or deionized water is to be used

7 Mix thoroughly after dilution

8 Light sensitive reagents are to be stored out of the light

pressure bleed hole

sample

heat

Figure 19

26 RECREA TIONAL DR UGS

ACETIC ACID 1.0%

Pipette 1 ml of glacial acetic acid into a 100 ml volumetric flask Dilute to volume with waterand mix

ACETIC ACID 10%

Measure 100 ml of glacial acetic acid and transfer to a 1 L volumetric flask containing about

600 ml of water Mix, dilute to volume with water and mix again

Mix 200 ml of reagent grade ether with 100 ml of reagent grade acetone

AMMONIUM HYDROXIDE, DILUTE (0.5%)

Transfer 2 ml of concentrated (28%) ammonium hydroxide to a flask and add 98 ml of water.Keep no longer than 1 month

AMMONIUM HYDROXIDE 5%

Mix 20 ml of ammonium hydroxide (this is concentrated, 28%) with 80 ml of water Store in

a glass stoppered bottle

HYDROCHLORIC ACID 1 N

Add 8.4 ml of cone, hydrochloric acid to a volumetric flask containing 70 ml of water Dilute

to volume and mix

SODIUM CHLORIDE, SA TURA TED

Add 40 g of sodium chloride to 100 ml of hot water and mix

Prepare from a concentrated solution of sodium hydroxide that has been standardized, ml x N

= ml x N Standardize this dilute solution against a standard acid solution and adjust to 0.05 N

Weigh 100 g of sodium hydroxide pellets and transfer to a 1 L volumetric flask containing 800

ml of water Mix to dissolve, cool to room temperature, dilute to volume and mix

SODIUM HYDROXIDE 40%

Weigh 40 g of sodium hydroxide pellets and transfer to a pyrex 100 ml volumetric flaskcontaining 50 ml of water Swirl or mix to dissolve Cool to room temperature, dilute to volumeand mix again

28 RECREA TIONAL DRUGS

As you should have noticed, percentages are easy to figure out how much reagent to mix withyour water With the formula above and standardized solutions you can also figure the strength

in N measurement quite easily

CHEMISTRY HINTS

1 Before beginning any preparation, read carefully the entire method and also obtain a clear idea

of the theory as well as the entire practice of the operation Know the reason for every step

4 Procure suitable and sufficient apparatus This applies especially to the use of vesselsappropriate to the quantities to be used

5 Clean thoroughly and, if necessary, dry all apparatus before use (If a formula calls for anydry or anhydrous chemicals, solvents, reagents, etc., then even the humidity in the air should

be kept out of the reaction.) Scrub stubborn residue with acetone and a bristle brush, thenuse soapy water, and rinse thoroughly with water

6 Fit apparatus together carefully and compactly, paying particular attention to the clamping thatholds the apparatus steady and to the fitting and boring of corks and stoppers

7 Adhere to the instructions given with regard to definite times, temperature and weights

8 Develop a habit of observation; notice all changes and remember or record them This maylater tell you what you are doing wrong if the reaction fails

9 Take and test samples whenever advised or convenient to do so

10 Remember that the criterion of practical work is the yield of pure substance obtained, and

if this differs by more than 10% from the yield stated, seek the cause of this difference, andthen repeat the process

11 Test a sample of the product's properties and characteristics (melting point, boiling point,weight) Cocaine and most of the other drugs will have specific tests that should be performedalso to determine purity and potency

12 Cost of the preparation (see apparatus section) Do get a good idea on the cost of a particularformula, make a list of chemicals and apparatus necessary, then call a supply company (seesuppliers section) and get prices of the items As a general rule, don't start something youcannot afford to finish

13 Keep bench and work area clean and uncluttered When you are finished using a chemical,put it back into storage and even if you are not finished with it, seal it back up with the cap

or stopper A clean work place makes things much faster, easier and safer

14 Special Note: Never, under any circumstances attempt to make any drug using any of the

formulas from this book Find the reference given in a library and copy the said formula fromthe Journal only by a copy machine The publisher and myself are human and may have made

Distillation 29

an error in spelling, printing, etc Any small error may make the difference between drugs andpoisons If you cannot get to a decent library call or write one and for a small fee they willsend you copies of the desired section of the Journal

30 RECREATIONAL DRUGS

REDUCTIONS

Since this is the most important step in the production of amphetamines, I have created a specialsection describing the preliminaries and techniques in great detail After spending a lot of timeand money to synthesize your nitropropene, you will be greatly disappointed to find that followingthe directions given in a journal is not enough to create an active compound There are someminor pitfalls that many scientists figure all their readers already know about, but if they don'tknow about them, their reduction will fail miserably, wasting the their time and the chemicalsinvolved

Although many formulas listed are designed specifically for reducing to amphetamine typecompounds, they should work well on other drug synthesis calling for reductions After finding

a suitable or compatible reduction formula, replace the nitrostyrene or nitropropene, etc., with

an equimolar ratio of the compound you wish to reduce If I explained everything that I wouldlike you to know about reductions, this chapter would be about 200 pages longer than it alreadyis; obviously I cannot say everything, so I will stick with the basics

Reductions in organic chemistry utilizing zinc, iron, and hydrogen sulfide, have been performedsince the 1840's Catalytic hydrogenation came about in 1897, and reduction with metal hydridescame into usage in 1947

REDUCTIONS WITH METAL

Zinc Next to sodium, zinc is the most used reductant It is available in powder, dust, and

granular (mossy) forms Zinc gets coated by a layer of zinc oxide which must be removed toactivate it before it can reduce effectively It can easily be activated by shaking 3 to 4 min in

a 1% to 2% hydrochloric acid solution This means for every 98 ml of water volume, add 2 ml

of coned hydrochloric acid Then wash this solution with water, ethatiol, acetone, and ether Otactivation can be accomplished by washing zinc in a solution of anhydrous zinc chloride (a verysmall amount) in ether, alcohol, or tetrahydrofuran Another way is to stir 180 g of zinc in asolution of 1 g copper sulfate pentahydrate Personally, I like the HC1 acid method

Mossy zinc is activated by converting to zinc amalgam by brief immersion in amalgam solution.(Use 40 g mossy zinc immersed in 4 g mercuric chloride, 4 ml concentrated HC1 acid, and 40

ml of water.) This type of amalgam can be used with powdered zinc also

Reductions with zinc are very effective on aromatic nitro compounds using organic solventsand an acid medium at around 50-70°, No matter what kind of metal is used, good stirring is

a must After the reaction is over, the zinc is filtered off, care being taken not to let it becomedry, as it is pyrophoric Also, be careful while disposing of zinc for the very same reasons

Reductions 31

Zinc Reduction (This is a mild procedure used with great success on highly ring substituted

derivatives.) CPB, 16(2), 217

53 g of nitrostyrene (or equimolar amount of nitropropene) and amalgamated zinc (made from

min of agitation, decant the liquid off and use the wet zinc immediately) are suspended in 2 liters

of ethanol Under vigorous stirring, add coned hydrochloric acid until the yellow coloring of thereaction disappears (check by spotting on filter paper and allow to dry) Stir for an additional

30 min after the yellow color is completely gone, filter the zinc off, evaporate the ethanol off(alcohol smell will be gone after shaking), and pour residue into 1 liter of water The aqueoussolution is made alkaline with coned ammonium hydroxide after being washed with ether The

oily substance This is recrystallized from an acetone ethanol mixture to give the product ahydrochloride form

Another Zinc Reduction Prepare amalgamated zinc by treating 50 g of zinc with 5 g of

mercuric chloride as above Agitate the activated zinc in 100 ml of methanol using an ice bath(ice baths are actually ice water baths) Add to the above solution a small portion of hydrochloricacid, then a portion of the nitrostyrene (20 g) in 200 ml of tetrahydrofuran The acid (in small

amounts) and the nitrostyrene solution are added alternately with cooling to hold temp below

50° After the styrene is completely added, check to see if the reaction mixture has lost the yellowtint by spotting on filter paper; add more small amounts of HCL acid if you can see a yellowtint Filter the zinc off, remove the methanol tetrahydrofuran mixture by distilling in vacuo Pourthe residue into 500 ml of water (water is always distilled), wash with ether, basify with coned

pale-yellow, oily compound (9.5 g) that is recrystallized from ethanol

Another Zinc Reduction Prepare or activate the zinc as follows: 400 g of mossy zinc is treated

with 800 ml of 5% aqueous solution of mercuric chloride for 1 hour Decant the solution off anduse the zinc right away Add 834 mole of compound to be reduced to the zinc amalgam, followed

by as much HC1 acid (.834 mole) diluted in as much water as is required to cover all the zinc.Reflux for 6 hours while adding small portions of dilute HCL acid Cool, separate the upper, washfree of acid (a few portions of dilute sodium hydroxide), dry and distill to get about a 79% yield

of product

Magnesium Halogen derivatives, like bromides, iodides, and imidoyl chlorides, react with

magnesium to form Grignard reagents Grignard reagents decompose with water or dilute acids

to give compounds in which the halogen has been replaced by hydrogen This replacement canalso be carried out by the simultaneous action of isopropyl alcohol and magnesium activated by

the addition of iodine (see Wakefleld, Smith, Org Syn Coll., Vol 5, 998 (1973) A magnesium amalgam can also be prepared to carry out certain reductions (see Adams, Org Syn Coll., Vol.

1, 459 (1932) One thing to remember is that the entire operation must be kept dry This requiresthe use of dry reagents, and no atmospheric H20 is to enter the reaction, until the Grignard reagenthas finished the job

To prepare the Grignard reagent All reagents must be thoroughly dry and the magnesium must

be cleaned To clean magnesium ribbons or pieces, sand thoroughly all the faces and edges withemery cloth Wash free from sandings with ether and dry in oven at about 109° Dry your reagentsthis way; allow your methyl iodide (or ethyl iodide, or n-hexyl bromide, or lauryl bromide, or2-Br-heptane, or any other analog that your formula may specify) to stand over night, or for 12hours over calcium chloride, and distill to purify Dry ether as specified in the precursor and

32 RECREATIONAL DRUGS

reagents section of this book, or purchase dry Here is a typical formula for preparing and using

a Grignard reagent

36 g (1 mole) of methyl iodide (or 1 mole of specified analog) are mixed with 50 cc of dry

ether 20 cc of this mixture are run into a flask fitted with a long reflux condenser and an additionfunnel 6 g of clean magnesium (this can be purchased by the block, and after sanding a side,clean chisel or cut thin shavings off, wash and dry as above) are placed in the reaction flask beforethe 20 cc of the iodide-ether mixture are run in It is sometimes necessary to add a crystal ofiodine to start the reaction or to reduce the more stubborn compounds, e.g,, the nitriles leading

to Amidone When the reaction first subsides, add 70 cc of dry ether and run the remainder ofthe methyl iodide-ether solution into the reaction flask one drop at a time from the addition funnel

After the addition, reflux or boil gently on water bath until all, or almost all, the magnesium hasdissolved

Rig down the apparatus, and with external ice cooling, add 1 mole of the compound to bereduced (e,g., the high or low melting nitrite intermediate for Amidone or 3, 5 dimethoxybenzamide or 3, 5 dimethoxy benzaldehyde for THC formulas, etc.), after mixing with an equalvolume of dry ether, by dropping in with an addition funnel while shaking or stirring Allow tostand for 12 hours after the addition This last paragraph and the one to follow describe a generalmethod If you have specific or special instructions regarding the addition and removal of yourcompound, by all means use those If you have no special instructions (e.g., react with Grignardreagent or react with ethyl-Mg-bromide) then use ethyl bromide or a suitable analog and follow

the procedure given here

While stirring and cooling, add just enough dilute HCl acid to dissolve the precipitate (Note:

different acids in different concentrations are sometimes used) Separate the aqueous layer and

wash the ether with sodium bicarbonate solution and sodium bisulfite solution (in that order;bisulfite removes free iodine) and again with sodium bicarbonate solution Dry over suitabledrying agent and evaporate or heat gently (in dry atmosphere) to remove the ether Purify byfractional distillation,

Aluminum Reductions with aluminum are not commonly found, however, I have included

the preparation of the amalgam Aluminum can be used to reduce aromatic nitro compounds(Org, Syn., 52, 77(1972)

Aluminum Amalgam Immerse thin strips of aluminum foil in a two percent aqueous solution

of mercuric chloride for 30-60 seconds Use a big bowl and plenty of solution for a moderateamount of foil Decant off the solution, rinse the foil strips with dry ethanol, ether, and cut theminto pieces of about 1cm2

Iron, Iron reductions have been used for over 130 years About the only reductions using iron

are those for aromatic nitro compounds They are not used much these days in drug synthesis,

so I will not elaborate further

Tin, If you should happen to run into a reduction using tin, prepare the following amalgam

as follows

Tin Amalgam To a solution of 15 g of mercuric chloride in 100 ml of water, add 100 g of

30 mesh tin metal while stirring briskly Let set for a few seconds after several min of stirring

to see if the tin has acquired a shiny coating of mercury; if not, stir or shake for 30 sec moreand check again Decant the liquid and wash the tin amalgam until the washings are clear Thiscan be stored under distilled water for a moderate amount of time

Reductions 33

Catalytic Hydrogenation General statements about catalytic hydrogenation are difficult to

make since the results are affected by many factors such as the catalysts, activators, inhibitors,solvents, pH of the medium, temp, and pressure

T-l Raney Nickel Catalyst To prepare, proceed as follows: in a one liter three necked flask

containing 600 ml of a 10% sodium hydroxide solution, 40 g of Raney nickel aluminum alloy(50%) is added in small portions During the addition the temp should be 90-95° and there should

be good stirring (do not use a magnetic stirring device) After the addition is complete (25 to

30 rnin), stir for 1 hour more, and let the nickel settle to the bottom of the flask Decant thesolution off, wash with 5 times 200 ml of water, 5 times 50 ml of ethanol, in such a way tokeep the nickel always covered with liquid The catalyst must be stored under ethanol andrefrigerated It may be stored for three months and remain active

General Method of Hydrogenation Using Raney Nickel This method may be altered to use

larger formulas If you have a formula giving specifics, then use it Using a Parr low pressurehydrogenation bottle is recommended 0.1 to 0.4 mole of the compound to be hydrogenated issuspended or dissolved in 30-80 ml of ethanol 5-10 g of the above catalyst is added with goodstirring, followed by 1-2 ml of 20% NaOH solution The hydrogenations are carried out at 40-50° and 40-50 psi The reduction product is separated and purified depending on its physicalproperties

Method of Hydrogenating With Raney Nickel Catalyst This method gets the hydrogen

atmosphere from the NaBH (sodium borohydride) that is added directly to the mixture instead

of piping the hydrogen in It is useful for converting phenylacetonitrile into the correspondingphenethylamine 40 g of phenylacetonitrile in 90 ml of methanol are stirred and 10 g of the aboveprepared catalyst, or nickel analog, are added With good stirring, add dropwise, over ten min

a solution of 7.6 g NaBH in 25 ml of 8N sodium hydroxide with external cooling to keep temp

methanol to get the amine (See "precursors" to make phenyacetonitrile.)

A Different Method JMC, 14, 375 (1971) A solution of 16 g of phenylacetonitrile (see

methadone in the analgesics chapter for the formula to diphenylacetonitrile which may work here

are placed in a 300 ml stirring autoclave, or a pressure cooker that has a glass or ceramic liner

(these are sometimes referred to as bottles and can be purchased at most any welding or gassupplier) Make sure your fittings and lines are tight and capable to withstand the pressurerequired Stirring or shaking and heating to 125° for two hours follows immediately after thehydrogen pressurization Filter, evaporate the methanol and distill in vacuo the residue, savingthe fraction at 110-115° at 0.4 mm of vacuum To get the hydrochloride form, add the above

cm2 - 1500 p.s.i

Platinum Platinum oxide is the most common catalyst although there are others This is a

brown, non-pyrophoric, stable powder made from fusing chloroplatinic acid and sodium nitrate

It is considered among the most powerful catalysts, each molecule of this catalyst requires twomolecules of hydrogen, and this amount must be subtracted from the final volume of hydrogenused in exact hydrogenations It is suitable for almost all hydrogenations, being able to stand strongacids Platinum catalysts are more effective and easier to buy than to make

34 RECREATIONAL DRUGS

Platinum Reduction for Reducing Ketones or Aldehydes JACS, 70, 1316 (1948) This is a

good, easy method requiring little pressure In a 300 ml Parr hydrogenation apparatus containing

10 ml distilled water, 0.2 g of platinum oxide is reduced to platinum by shaking in a hydrogenatmosphere for ten min Other catalysts can be substituted; if they are not an oxide then this firststep should be unnecessary Benzylmethyl ketone (0.3 mole) or phenyl-2-propanone, or analogs(see precursor section for intermediates synthesis), 20 g (0.37 mole) of ammonium chloride, 225

ml of dry methanol that has been saturated with ammonia, and 25 ml of aqueous ammonia areadded together and reduced by shaking with one to three hydrogen atmospheres Good shaking

is required during this operation and is continued until the pressure remains constant indicatingthat the reduction is complete Filter after venting and wash the solids in the filter paper withwater or methanol to get all the product into the filtrate Reflux the filtrate to remove the excessammonia With the ammonia removed, the solution is cooled, acidified to congo red paper with

coned HC1 acid, and evaporated to Vi its volume under vacuo.

Add 200 ml of water and extract with 3 times 25 ml of benzene Discard the benzene extracts

as they do not contain product The remaining aqueous solution is made strongly basically with50% NaOH solution An oily layer and a water layer will form Separate the layers and extractthe water layer 3 or 4 times with ether Combine the ether extracts with the oily layer and washwith water Fractionally distill to get purified phenethylamine Yield: 69%

Another Hydrogenation with Platinum Oxide JACS, 55, 2694 This method is used to reduce

those hydrox-mandelonitriles in the amphetamine section It uses low pressure and can be used

on about any reducible compound It can also use palladium oxide as the catalyst A solution

of 35.8 g of phenyl-2-propanol in 250 ml of 80% ethanol containing 7.3 g of HC1 is hydrogenatedfor 3 hours in a Parr hydrogenation bottle at 3,5kg/cm2 or 50 p.s.i, over 0,5 g of platinum oxide(or palladium oxide; Raney nickel may also work) or an equimolar ratio of analog catalyst forabout 3 hours Filter off the catalyst and rinse with a little water to wash all the product fromthe catalyst Dilute the filtrate to 1 liter of volume with water and extract twice with ether toremove any acid insoluble material The ether extracts do not contain product The aqueous layer

is made alkaline with solid NaHCO3 to a pH of 8-9 and the basic oil which separates is extracted

evaporated to remove the ether To convert to the oxalate, add ether to the crude product andadd to a solution of 9.6 g of oxalic acid dihydrate in a small volume of methanol Give ampletime to crystallize and then recrystallize from methanol Yield: 31.2 g, mp: 134-135° Yield:

-wvonovxv tonvcrxing to the oxalale, 27.5 g, mp; 54-55°.

Palladium Palladium catalysts are much like platinum, but a little more versatile Palladium

oxide is made by heating palladium chloride with sodium nitrate to fusion at 575-600° Usepalladium oxide (an equimolar amount) in the formulas already given for reducing with platinumoxide Below is a reduction with palladium-carbon

Reducing With Palladium-Carbon Dissolve 0.02 mole of nitropropene or nitrostyrene in 250

ml glacial acetic acid Add one gram of palladium-carbon catalyst (or analog) followed by 10

ml of coned sulfuric acid Reduce at 2 atmospheres by admitting hydrogen from bottle It shouldonly take about 15 min to complete, filter, add 36 ml of 5N NaOH and evaporate in vacuo toget the amine (I am not sure if this is purified, good enough for me to take.) For another catalyticreduction of nitropropenes see JOC, 37, 1861 (1972)

A Different Nickel Catalyst This can be used instead of Raney nickel catalyst It is effective

and cheap and it does not cause suspicion with the law

Reductions 35

Make a solution of 1.25 g of powdered nickel acetate in 50 ml of 95% ethanol in a 250 mlflask Add 5 ml of 1M solution of sodium borohydrate in 95% ethanol at room temp Stirring

is continued until gas stops evolving (about 30 min) The flask along with the colloidal substance

is now used directly in the hydrogenation

A General Method For Making Raney Nickel Catalyst Mix an alloy consisting of 50% nickel

and 50% aluminum (they should be clean and pure) To make the catalyst stronger use lessaluminum, but never use under 11% Add the alloy to 25% to 50% sodium hydroxide watersolution and heat to 50-100° Wash with plenty of water (always use distilled water in an organiclab) and then with ethanol as instructed in the T-l catalyst described above These catalysts arepyrophoric and should never be allowed to dry once prepared Store under ethanol The T-l isabout the strongest, using the 50/50 alloy rereacted with another 50% aluminum

addition funnels stirring

device

hydrogen generator

magnetic stirring device

safety

discharge

Hydrogenation Apparatus

Apparatus for Hydrogenation at Atmospheric Pressure

Without any idea of what hydrogenation apparatus should look like, carrying out the processwould be rather difficult Along with the pictures are general instructions for proper procedure

If you are following a specific formula then you may need to change things around to producethe desired product

Catalytic Hydrogenation by Generating Hydrogen From Sodium Borohydride The reaction and

generator flasks should be 500 ml size The reaction flask is charged with 100 ml of ethanol, 5

ml of a solution of 0.2 M chloroplatinic acid, and 5 g of activated charcoal, and if possible, theentire apparatus is flushed with nitrogen The addition funnel over the H2 generator is filled with

in 20 ml of ethanol is added to the reaction flask with vigorous stirring to prepare the catalyst

5 ml of coned HC1 acid are added to the generator flask; insert the addition funnel back into

36 RECREATIONAL DRUGS

you may add a solution containing 0.5 mole of the compound to be reduced to the reaction flask

making sure that you have closed all valves and have no leaking joints The discharge line (X)

is an indicator that keeps excessive pressure from blowing the apparatus apart It should not be

immersed too deeply into the mercury, and will allow bubbling if pressure is getting too high.(If the line can be immersed deeply into the mercury without destroying the apparatus, then this

sometimes be added to the reaction directly, therefore eliminating the need for a generation flask.Use (HCA, 53, 50) above formula utilizing Raney nickel and atmospheric pressure and theapparatus without the generation flask

There are many scientific supply stores that sell some very nicely engineered glassware designed

to do this job perfectly It is expensive and so I have shown the low budget type of set up The

flasks still need to be high quality and vacuum proof, as is the tubing and connection hosing.Clamp the hosing and use a mercury type seal on the stirring device; magnetic stirring devicesshould not be used with metallic catalysts as they conglomerate the catalyst to the stirring bar

by magnetic force

If your apparatus blows apart with regularity, replace mercury with water, but use a water trap

Hydrogenation at Medium Pressure This costs more to get started, but it is cheaper than NaBH4

if used on a large scale The best equipment needs to be used, with no skimping A regulatorshould be used on any gas coming from a high pressure tank (bottle) into a reaction apparatus

of any type, A stainless steel bomb of about 500 ml can be ordered or made by most any metalfabrication company for less than a chemical supplier Make sure these outfitters know that the

pressures required are up to 150 atmospheres Use standard high pressure fittings, valves, hoses

NOTE:

All fittings must be high pressure

gauge high

hose (optional)

high pressure hose

to allow shaking

and tubing

After assembling the apparatus as shown,

using teflon tape on all threaded parts

(includ-ing the cap fitt(includ-ing) and tighten(includ-ing all threads

until they are buried deeply into the fittings,

the apparatus must be tested This test must be

performed before every use Attach the high

tank regulator Pressurize to about 100

atmos-pheres (at least 25 atmosatmos-pheres more than

what you intend to use for your hydrogenation

product) Make sure both the inlet and outlet

valves are closed tightly and watch the gauge

for about 10 min to see if pressure drops If

pressure will not remain constant you have a

leak and it must be fixed before attempting to

perform the hydrogenation Use soapy water

to cover unions and valves to find the leak

After passing the pressure test, bleed off

hydrogen very slowly by opening the discharge valve and watching the gauge closely, stop openingjust as soon as pressure begins to drop The discharge hose does not need to be high pressure,

threaded union' for access (lube lightly with vaseline)

container (to hold) brake fluid

hot plate

Reductions 37

catalyst, compound to be hydrogenated, and with solvent if required Again use teflon tape and

retighten the cap fitting securely Pressurize to 75-100 atmospheres and see if the pressure dropsimmediately If so you have a leak and it needs to be fixed After a few min (no more than 6)

a small decrease in pressure must be noted to indicate that the reaction is processing Close inletvalve and bleed off pressure through the outlet to flush apparatus of air that entered while youcharged bomb with catalyst Perform hydrogenation as per the instructions of your formula

The pressure rating of your formula must be well below the pressure rating of your apparatus

as exothermic temp raises the pressure considerably Vigorous shaking should be performed fromthe time flushing is finished until the reaction is complete Mechanical devices can be rigged up

to save your arm wear When the pressure no longer rises or falls, this indicates that the reaction

hydrogenation fails, you may try again at a higher temperature

Some formulas call for elevated temperatures This can be accomplished by using an oil bath

due to the rise in temp After the temp has stabilized, any drop in pressure indicates that

is evident at that same temp After you are sure the hydrogenation is finished and the pressure

is bled off completely through the discharge valve, check to make sure the hydrogen tank andregulator are both closed tightly Now and only now are you allowed to disconnect the bomb.Filter the contents of the bomb and rinse several times with small amounts of suitable solvent.Use these bomb rinses to wash product from catalyst as it sits on the filter paper, using care tokeep pyrophoric catalysts wet at all times Work the filtrate up as required for the properties ofyour specific product

Note: After you have pressurized the bomb and closed the inlet valve to perform the

hydrogenation, you must remember to close the master valve on the hydrogen tank Also thosehuge cylinders (bottles, tanks) that you see on welding apparatus are not required, as smaller tanksare available and they contain more than enough pressure to do the job

Hydrogenation at High Pressures These are carried out almost exclusively in autoclaves.

Autoclaves are much like the apparatus previously shown, but with much more steel to withstandthe high pressures and temperatures they receive Most of them have built-in heating elementsand temperature indicators Yes, they are very expensive, I have seen some homemade units that

functioned quite effectively but I do not recommend that you try to build one If you do try to

build one, know what extremities the unit will be subject to and get professional advice andassistance for construction Because medium and no pressure hydrogenations are so effective, Iwill not elaborate on high pressure systems any further

REDUCTIONS WITH HYDRIDES

This requires a little knowledge in handling before attempts are to be made at reducing Hereare some things to remember

1 Sodium borohydride and sodium cyanoborohydride have been known to explode uponremoval of a screw cap from a glass bottle

2 Lithium aluminum hydride should be stored in polyethylene bags, not ground glass bottles

38 RECREATIONAL DRUGS

3 Lithium aluminum hydride squeezed, or smashed, may cause a fire

4 Contact of lithium aluminum hydride with water may cause fire or explosion

5 Borane (sometimes called diborane) ignites when in contact with air, so it must be coveredwith tetrahydrofuran, always

6 Contact with water may ignite sodium aluminum hydride

A Typical Lithium Aluminum Hydride Reduction JACS, 72, 2781 (1950) To a well stirred

mixture of 53 g lithium aluminum hydride (LAH) and 2500 ml of dry ether is added 55 g of4-hydroxy-3-methoxy-B-nitrostyrene (or equimolar ratio of nitropropene or analog) in 150 ml

of dry ether over an hour and 20 min Stir and reflux for about 9 hours, taking care to excludeall moisture Cool and add 3000 ml of ice cold 1.5 N sulfuric acid dropwise with good stirring(the acid addition can be speeded up after about half of it has been added) The water layer isseparated and its pH adjusted to 6 with solid lithium carbonate This solution is heated to boilingand the aluminum hydroxide that precipitates is filtered off The hot filtrate is mixed with asolution of 70 g of picric acid in the minimum amount of hot ethanol that it takes to dissolvethe picric Let stand for 4 hours, filter and recrystallize from water

88 g of the above picrate product in 1 liter of water is mixed with 400 ml of coned hydrochloricacid The picric acid which precipitates is filtered off and the filtrate is extracted with nitrobenzeneand then with ether (extra ether extracts may eliminate the need for nitrobenzene) The aqueoussolution is evaporated (reduced pressure is fastest) to dryness, dissolved in methanol-ethyl acetate,and filtered hot You may filter off the crystals before they reach complete dryness if you wouldlike to sample a little while waiting Yield, 90% This is a gentle reduction made from Tyramine,but it can be used on most any reducible forms See the amphetamines chapter for formula (JACS,

72, 2781, 1950) of 4-hydroxy-3-methoxy-B-nitrostyrene and analogs For a reduction using thereverse addition of LAH and several other reductions see the amphetamine chapter

A Reduction With Aluminum Hydride (Alane) In a three necked 1 liter flask equipped with

a gas tight mechanical stirring device, an addition funnel, and a long reflux condenser, is chargedwith 0.1 mole (3.8 g) of LAH and 100 ml of dry ether Add a solution of 0.1 mole (13.3 g)

of aluminum chloride (dry or anhydrous) rapidly through the dropping funnel, continuing thestirring the entire time After five min, add 0.1 mole (16.3 g) of nitrostyrene, or analog (seeamphetamines section), in 200 ml of ether to the well stirred reaction, dropwise One hour afterthe nitrile addition add dropwise enough water (until the bubbling stops) to decompose the excesshydride (or halide) Then add 140 ml of 6 N sulfuric acid diluted with 100 ml of water Separatethe ether layer and extract the aqueous layer with 4 100 ml portions of ether After cooling theaqueous layer is alkalized with powdered KOH to pH 11, diluted with 600 ml of water, andextracted with four 100 ml portions of ether The combined ether extracts are stirred with Drieriteand evaporated under reduced pressure The residue (21.5 g) is distilled to give correspondingproduct Although there is no reference for this method, the yield is 90%

Sodium Reductions, Reductions using sodium are becoming increasingly rare, but they do exist.

In case you should find a formula requiring a sodium amalgam, I have given the preparation

Sodium Amalgam 5 g of clean sodium are cut into 3-5 mm squares Each individual cube

is placed on the surface of 245 g of mercury in a dish and held underneath the mercury with

a glass spoon until dissolved The remaining sodium cubes are treated the same way, as soon aspossible After the sodium has been added, the mixture is allowed to cool, solidify, and then iscrushed Store in a closed bottle

Reductions 39

This reaction is highly exothermic, so heat is normal If the formula does not specify the sodium

amalgam then do not use it (e.g., the first formula in the amphetamines chapter).

Reduction with LAH and Aluminum Chloride This gives some of the best yields possible, of

all reductions known to me It is designed to reduce phenylacetonitriles but may also be used

to give high yields with reductions of nitropropenes, etc It is used for reducing diphenylacetonitrile(see analgesics, the Amidone formula, for the synthesis of diphenylacetonitrile), to givediphenylethylamine; however, phenylacetonitrile may also be used to give phenethylamine (seeprecursors section to get several different formulas for phenylacetonitrile)

JACS, 77, 2544 (1955) In a 1 liter 3 necked flask fitted with a mercury sealed stirrer, a reflux

condenser, and an addition funnel, is placed a solution of 0.1 mole of LAH in 100 ml of dryether Through the dropping funnel, a solution of 0.1 mole (13.3 g) of aluminum chloride in 150

ml of dry ether, is added to the LAH solution rapidly Next a solution of 0,1 mole (19.3 g) ofdiphenylacetonitrile (or an equimolar amount of analog) in 200 ml of dry ether is added dropwise

to the well stirred mixture An evolution of hydrogen should be noted After the addition iscomplete, continue stirring for 1 hour, then add water to decompose the excess hydride Add 140

ml of 6 N sulfuric acid and 100 ml of water Separate the ether layer and extract the aqueouslayer in an ice-water bath and add KOH until the pH is 11, then extract with four more 100

ml portions of ether after diluting with 600 ml of water Combine the ether extracts, dry overDrierite and evaporate the ether off Fractionally distill through a 12 inch column at about 184°using 17 mm of vacuum Yield: 91%

Note: Always add water slowly to hydride type substances when decomposing them; when

bubbling stops they are usually decomposed